From Samstein et al., Nat Genet 2019
Sequencing: MSK-IMPACT (Next Generation Sequencing).
Panels Used:
Note: Higher mutation counts detected as more genes are analyzed.
Datasets:
survivalSurv()
survfit() (Kaplan-Meier).clinical_patients.survivalfgseaMultilevel() from fgsea package.Structural Variants (SVs) are large-scale genomic rearrangements that can significantly disrupt gene function.
EGFR is the most significantly overrepresented gene when aggregating both the beginning and ending sites of the SVs.
EGFR is a receptor tyrosine kinase frequently altered in cancer. Its activation drives uncontrolled cell growth and proliferation. *
* From Yarden & Sliwkowski, Nat Rev Mol Cell Biol 2001
EGFR is not a primary mutational target
Alternative Pathways: Genes like TERT and TP53 show a much higher incidence of pinpoint mutations.
→ distinct biological pathways compared to the SV-driven EGFR pathway.
Significant Pathways in Glioma
| Biological Process | pvalue | adjusted pvalue |
|---|---|---|
| GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT | 1.87e-06 | 0.00018 |
| GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS | 3.91e-07 | 0.00018 |
| GOBP_REGULATION_OF_APOPTOTIC_SIGNALING_PATHWAY | 8.07e-07 | 0.00018 |
| GOBP_REGULATION_OF_CELLULAR_LOCALIZATION | 1.65e-06 | 0.00018 |
| GOBP_REGULATION_OF_MITOTIC_CELL_CYCLE_PHASE_TRANSITION | 1.38e-06 | 0.00018 |
| GOBP_TUBE_DEVELOPMENT | 3.69e-06 | 0.00030 |
| GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS | 7.12e-06 | 0.00039 |
| GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION | 6.76e-06 | 0.00039 |
| GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION | 6.40e-06 | 0.00039 |
| GOBP_MITOTIC_CELL_CYCLE_PHASE_TRANSITION | 8.29e-06 | 0.00040 |
| GOBP_BLOOD_VESSEL_MORPHOGENESIS | 1.71e-05 | 0.00070 |
| GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY | 1.58e-05 | 0.00070 |
| GOBP_APOPTOTIC_SIGNALING_PATHWAY | 2.78e-05 | 0.00105 |
| GOBP_CELL_AGING | 3.01e-05 | 0.00106 |
| GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY | 3.40e-05 | 0.00112 |